CN104887388B - Anterior segment drug conveys - Google Patents

Abstract

The invention discloses a kind for the treatment of system, including eye insert, this insert is arranged on the region outside the visual zone of eyes.Eye insert includes two components：First frame member and the second buffer component.First component is used as skeletal frame, and it keeps positioning and offer supporting to second buffer component of the implantation piece along ocular region part.The first component causes treatment system to remain mounted on the front part of eyes at least 30 days.In certain embodiments, first component keeps constant dimensions and shape, such as annular, the ring or shaped form ring with haptic element, it is determined that to be engaged with bottom and the constraint of top conjunctival cul-de-sac, implantation piece to be maintained in tear fluid and/or against eye tissue.

Description

Anterior segment drug conveys

The present invention is that Chinese invention patent application number is 201080031182.9 (PCT/US2010/037268, international applications Day be on June 3rd, 2010), the divisional application of entitled " anterior segment drug conveying ".

The cross reference of related application

This application claims U.S. Provisional Patent Application No.61/183839 priority, the U.S. Provisional Patent Application The No.61/183839 applying date is on June 3rd, 2009, and entire content of this document is incorporated herein by reference.

Technical field

The present invention relates to the component for eye therapy, system and method.Example embodiment is provided for drug delivery Eye insert and use the method for being positioned at eye insert on eyes leading portion or near leading portion.Example insert can be Preceding surface of the outside of visual zone along eyes is worn, and the horizontal feed one or more medicine that can be treated with safety and effectively Thing at least 30 days.

Background technology

A variety of ophthalmology and non-eye disease need multi-medicament supplying eyes.Eye drops and gel can be active drugs Delivery vehicles, but also have the shortcomings that obvious.Specifically, eye drops mixes with the fluid in tear film, but can be with Residence time only has 2-5 minutes in tear film.Only 5% medicine can absorb on the spot, some or all remainders Bring into lacrimal from lachrymal sac, and be finally absorbed into blood flow.At least two unfavorable effects may be had by being absorbed into blood flow：The One, most of drug waste；Second, medicine is present in blood flow may bring harmful secondary work to the remainder of body With.Gel more effectively can be adhered on eyes, but may also cause the eye-blurred of patient for a long time.Controlled for some Treat, eye drops and gel are required for frequently repeating application.Therefore, it is also desirable to a kind of improved method that medicine is conveyed to eyes, The medicine will not leave its target location, it is not required that frequently repeat application.

The shortcomings that in view of eye drops, it is known that a variety of alternatives have been proposed.Wherein, the known of eye drops replaces For mode include by comprising or be impregnated with the component of medicine and be arranged in therapeutic scheme below eyelid.

Such solid eye medicine type obviously has obvious potential advantage compared with the eye drops drug treatment of eyes. Particularly, medicament for the eyes conveying implantation piece can help to overcome relatively low patient's biddability of traditional eye drops and other medicine types, very The problem of active drug absorption existing for difficult application and frequently mistake application and eye drops is limited, while be advantageously possible for advanced The favourable application and introducing of polymer chemistry processing are general from other known delivery system release maintenance/control medicine Read.

Although drug delivery implantation piece has very big potential advantage, medicine is still mainly applied to by eye drops The front portion of eyes.May limit existing eye insert Receptive factor include they comfortableness it is poor, they be easy to ring Around eyes are mobile or motion, they excessively introduce unfavorable repulsion in sleep procedure or the friction of eyes, they and eyesight Interference, and/or it is difficult to drug delivery implantation piece known to arrangement and taking-up.

In view of the above situation, new delivery device, system and method will be particularly conducive to therapeutic compounds is defeated Deliver to the leading portion of eye.It will particularly advantageously provide improved eye insert, so that doctor and user are acceptable, and should Preferably insert is easily inserted and removed from so that patient comfort, it is nontoxic and do not interfere eyesight or Oxygen permeation, can have and can weigh Multiple released movement, and/or easily manufactured with reasonable prices.

The content of the invention

The invention provides a kind for the treatment of system and method for conveying at least one medicine.Example embodiment passes through insert And one or more medicines are conveyed to the front part of eyes from eye insert.

In a first aspect, the embodiment provides a kind for the treatment of system.The treatment system includes eye insert.Eye Insert is arranged on the region outside the visual zone of eyes.Eye insert includes two components：First frame member and Two buffer components.

First component is used as skeletal frame, and it keeps positioning and offer of the implantation piece along ocular region part slow to second Rush the supporting of component.The first component causes treatment system to remain adhered on the front part of eyes at least 30 days.At some In embodiment, first component keeps constant dimensions and shape, such as annular, the ring or shaped form ring with haptic element, and it is true It is set to and is engaged with bottom and the constraint of top conjunctival cul-de-sac, implantation piece to be maintained in tear fluid and/or against eyes group Knit.

In many embodiments, first component expansion or change shape, farthest to make it be attached to eyes Front portion structure on.Medicine can be dispersed in first component or in first component, or is dispersed in second component or second Have on component, or both.

In an exemplary embodiment of the invention, treatment system is designed for easily being inserted and removed from by patient.

Brief description of the drawings

Fig. 1-1 and 1-2 illustrates the anatomical tissue structure of eyes 2 for fitting through an insert to treat；

Fig. 2-1 illustrates the example embodiment of the treatment system including eye insert, and the treatment system can also include：Insert Enter device；Structural change material, the structural change material, which is dissolved, (or expands, dies down, tenses or performs some other drivings Mechanism), so as to which implantation piece is rearranged into deployment architecture from insert structure；Deng；

Fig. 2-2 and 2-3 illustrates the top view and sectional view of the treatment system shown in Fig. 2-1；

Fig. 2-4 illustrates the embodiment for the treatment of system, wherein, ring is included in two footpaths on the opposite segments on its surface To the projection or projection outwards and/or forward extended；

Fig. 2-5 illustrates the alternative embodiment of ring-shaped therapeutic apparatus system.In this embodiment, the storage of crescent or banana-shaped Storage is arranged on the low portion of eye insert.

Fig. 3-1 to 3-3 illustrates another embodiment for the treatment of system, and the treatment system includes annular construction member, the annular structure Part has at least 8mm diameter, is sized to fit within outside the visual zone of cornea, and the treatment system also has two or more More haptic elements；

Fig. 4-1 to 4-2 illustrates another embodiment for the treatment of system, in the treatment system, two or more concentric rings Shape component is kept together by four or more haptic elements；

Fig. 4-3 illustrates the embodiment using eccentric design, and so, one or more loop sections or segmental arc are present in ring Lower area in, so as to by target be delivered to eyes, tears can be easier aggregation region in (as in blind pipe)；

Fig. 5-1 to 5-3 illustrates the snakelike embodiment for the treatment of system, and the treatment system illustrates inflatable eye insert；

Fig. 6-1 and 6-2 illustrates another embodiment, wherein, the second buffer component includes two hydrogels being attached to each other Scleral contact lenses, to clamp the first rigid member between them；

Fig. 7-1 illustrates the enlarged drawing of the example eye insert of therapeutic system system, wherein, second component is arranged in first In the whole peripheral length of component；

Fig. 7-2 illustrates the sectional view of therapeutic system system, the therapeutic system system include with wedge-shaped outward flange and/or The second component of inward flange；

Fig. 7-3 illustrates the sectional view of therapeutic system system, and the therapeutic system system includes second with beveled edges Component；

Fig. 7-4 illustrates the sectional view of therapeutic system system, and the therapeutic system system includes second with rounded edges Component；

Fig. 8-1 illustrates the therapeutic system system with second component, and the second component can have preceding surface and/or rear table Face, the preceding surface and/or rear surface can also form the radius of curvature of eyes；

Fig. 9-1 illustrates the second buffer component, and second buffer component is arranged in the discrete length portion of the first supporting device On point；

Figure 10-1 and 10-2 illustrate one embodiment, wherein, coating surround second component local dissemination, so that the Two components preferentially expand in specific region；

Figure 11-1 illustrates the eye insert of annular, wherein, separate and/or relative part approaches or pressed from both sides at center Tightly, to form on-plane surface taco (taco) shape；

Figure 11-2 illustrates the annular eye insert being inserted into ocular surface, allows slowly to discharge in soluble material Before winding shape；

Figure 11-3 and 11-4 illustrate one embodiment, wherein, annular shape includes serpentine shaped or a series of elbows, this Sample, radially outer part or projection replace with radial inner portion；

Figure 11-5 and 11-6 illustrates alternative embodiment 88, wherein producing the cloverleaf pattern of three leaves；

Figure 11-7 illustrates the complete expansion eye insert being positioned in ocular surface；

Figure 12-1 and 12-2 illustrates two alternatives of the promptly instrument of change, its further groove or groove in end, with It is easy to the promptly device；

Figure 12-3 to 12-6 illustrates the different embodiments of the promptly pawl of instrument, and these are firmly grasped instrument and are changing into recessed Special shape on groove, to help by folding device into the shape of the form fit with eye, and illustrate the method using it；

Figure 13-1 to 13-4 illustrates the optional mode from promptly instrument release ring；

Figure 14-1 to 14-5 illustrates optional syringe shape insertion apparatus and the side for inserting annular eye insert Method；

Figure 15-1 to 15-3 illustrates another optional eye insert insertion apparatus of similar classical bicycle loudspeaker；

Figure 16-1 to 16-6 illustrates the optional insertion apparatus including flexible cone, outer rim supporting of the flexible cone along it Ring device, also illustrate using it eye insert to be placed in the episcleral method of eyes；And

Figure 17-1 to 17-2 illustrates the optional insertion apparatus including flexible bending band.

Embodiment

Fig. 1-1 and 1-2 illustrates the anatomical tissue structure of eyes 2 for fitting through an insert to treat.Eyes 2 include Cornea 4, iris 6 and white sclera 8.The conjunctiva layer 10 of substantially transparent covers sclera 8.Crystalline lens 12 is arranged in behind cornea 4. The retina 14 responded to light is located in the rear portion of eyes.Recess 16 is retina, provides sensitive focusing eyesight Part.Cornea 4 and crystalline lens 12 reflect light, to form image on recess 16 and retina 14.

Fig. 1-2 illustrates tear system 18, and the tear system 18 is responsible for producing and discharge tear fluid.Tear system is general including two Logical region：First, fluid is sent to eyes by lachrymal gland 20 and its excretory duct 22, the lachrymal gland 20 secretion tears, the excretory duct 22 Surface；Second, lacrimal 24, lachrymal sac 26 and nasolacrimal duct 28, they bring the tear fluid of transmission in nasal cavity into.

Fig. 2-1 illustrates the example embodiment for the treatment of system 30.Treatment system 30 includes eye insert 31, and can wrap Include：Insertion apparatus；Structural change material, the structural change material, which is dissolved, (or expands, dies down, tenses or performs some its Its drive mechanism), so as to which implantation piece is rearranged into deployment architecture from insert structure；Deng.In an alternative embodiment, insertion dress The driving of (or some other instruments) is put it is also possible that insert is rearranged into deployment architecture from insert structure, or can be with Insert is simply releasably held, to help to insert.In a further embodiment, eye insert before deployment, during Or afterwards and without obvious shape or other characteristic variations.But, eye insert is eventually positioned at the visual zone of eyes On outside region.Eye insert includes two components：First component 32 and second component 34.Fig. 2-1, which is illustrated, is arranged in eye Example treatment system 30 outside the visual zone of eyeball.

First component

First component is used as skeleton, and it substantially causes implantation piece to keep the position relative to eye structure, so as to be implanted into Part is attached on eyes, therefore provides the supporting for buffer component relative to ocular region part.Such first or skeleton Component is preferably to maintain treatment system and is attached on the front part of eyes at least 30 days.When medically wish or when patient wishes During prestige, treatment system can remove earlier than 30 days；But, for the viewpoint of physics, it can keep the preceding surface of eyes Eye insert at least 30 days.In certain embodiments, first component can continue to help whole implantation piece being maintained at eyes In 60 days or longer, 90 days or longer or even 180 days or longer, it is generally desirable to, all connect during whole such be implanted into Safely effectively healing potion conveys for continuous progress.Optional therapeutic system and method can benefit from the shorter implantation cycle, Can select one day or multiple days, at least several days, one week or longer, two weeks or longer etc..

Because it is used as the skeleton of the insert 31 for the treatment of system 30, therefore first component can determine the total of eye insert Shape.First component generally includes lametta, duroplasts such as nylon, PMMA, makrolon, poly terephthalic acid second two Alcohol ester and/or other polymer, polypropylene other can provide structure support so that treatment system remains adhered to Synthesis suture material on eyes.First component can also include coating plastic or metal, to cause coating to include medicine, Or make it easier to the second buffer element being attached on skeleton part.First component can be surface-treated, such as etc. Plasma etc., so that second component suitably can be attached on skeleton part.

Fig. 2-1 illustrates the basic embodiment of first component.Here, first component 32 is annular, straight with least 8mm Footpath, and be sized to fit within outside the visual zone of cornea, so that the eyesight not with patient is interfered.First component 32 Annulus preferably includes complete ring or anchor ring, but can also have some gaps along its periphery.In these embodiments, ring The curved angle of band will be more than 180 °.Fig. 2-2 and 2-3 illustrates the top view and sectional view of the treatment system shown in Fig. 2-1. The size for the treatment of system shown in Fig. 2-1 to 2-3 can must be bigger, to cause the edge of component to be arranged in the blind pipe of eyes It is interior.In treatment system by the example in the blind pipe of eyes, treatment system will be preferably manufactured at least two sizes, with Just different eye sizes (such as children VS adult, different adult human eye's sizes also may be selected) are adapted to.First component Optional shape be included in the shape of the insert shown and described in United States Patent (USP) No.3995635, the content of the document is by this Literary reference.

Fig. 2-4 illustrates the embodiment 36 for the treatment of system 30, wherein, ring is included in two on the opposite segments on its surface The individual projection radially outward and/or forward extended or projection 42.When blink when, eyelid by two projections " capture " eyelid it Between, and eye implantation piece is pushed back into its (otherwise this implantation piece energy in the therapeutically effective position outside the visual zone of cornea Enough on the surface of eyes slidably).

Fig. 2-5 illustrates the alternative embodiment 40 of ring-shaped therapeutic apparatus system 30.In this embodiment, crescent or banana Shape holder 42 is arranged on the low portion of eye insert.

Fig. 3-1 to 3-3 illustrates another embodiment 44 for the treatment of system 30, and the treatment system 30 also includes annular construction member, The annular construction member has at least 8mm diameter, is sized to fit within the outside of the visual zone of cornea, and the treatment system Also two or more haptic elements 46, each haptic element 46 are radiated to the blind pipe of eyes from annular construction member, are used to treat so as to provide The additional support point of system.Fig. 3-1, which is illustrated, is arranged in ring-shaped therapeutic system on the front portion structure of eyes, having haptic element System.Fig. 3-2 and 3-3 show respectively the top view and sectional view of an insert 44.

Fig. 4-1 to 4-2 illustrates the alternative embodiment 48 for the treatment of system 30, wherein, two or more annular concentric structures Part 52 is kept together by four or more haptic elements 50.Inner annular member has at least 8mm diameter, and size is set It is set to outside the visual zone for being assemblied in cornea.The outer annular member of next (and subsequent) has gradually bigger diameter, Outermost annular construction member preferably has at least 12mm diameter, and be sized to fit within the sclera of eyes, arched roof or blind Guan Shang.Fig. 4-1 illustrates the embodiment 48 for the treatment system being arranged on eyes.Before Fig. 4-2 is illustrated on insertion eyes Treatment system embodiment 48.The advantages of embodiment 48, there is provided the more high surface area for drug delivery, because depositing In two or more rings and four or more haptic element.Can be in the U.S. with the part shape that is additionally inserted into for improving surface area Seen in patent No.4540417, the content of the document is incorporated herein by reference.Fig. 4-3 illustrates the related implementation using eccentric design Example 49, to cause one or more annular sections or segmental arc 54 to be in the lower area of ring, so as to which target is delivered into eye Eyeball, tears be easier the region assembled, such as in blind pipe.This eccentric design is it is also possible that device is stable more constant Position, and hardly possible be rotated away from the position or move in the visual zone of eyes.In addition, target be delivered to it is blind Pipe can more effectively by some drug deliveries to nasolacrimal system (in addition to eye surface), such as when for nasal allergy medicine when.

In the above-described embodiments, first component generally remains constant size and dimension, such as annular or has tactile The annular of part, it is anchored/is attached on the barrier film, arched roof or blind pipe of eyes.

In other embodiments, first component can expand or change shape, to improve its front portion structure in eyes On attachment.Fig. 5-1 to 5-3 illustrates the snakelike embodiment 56 for the treatment of system 30, and it represents inflatable eye insert.Fig. 5-1 Illustrate the embodiment 56 being inserted in ocular surface；Fig. 5-2 illustrates embodiment 56 before insertion, and Fig. 5-3 is illustrated Embodiment in swelling state.The serpentine configuration of plurality of optional can be developed and be changed, described here to utilize Buffering and/or structural change technology, include United States Patent (USP) No.4540417 technology, and disclosure of the documents is joined herein Draw.

Relative to the embodiment of by the agency of, skeleton part can be formed as being consistent with the radius of curvature of eyes.

First component can expand when it absorbs the tear fluid in eyes, or can pass through spring effect machine Structure and stretch.The examples of materials that can be expanded when inserting in eyes includes PVPE, PVA and polyurethane gle.Bullet can be passed through The examples of materials that spring is acted on and stretched includes platinum alloy, titanium alloy, all stainless steel alloys and tempered metal, various clad metals And insulated wire.First component can include shape-memory material such as Nitinol, it can utilize thermal and magnetic or electromagnetic drive and from Martensite to austenitic state becomes suitable shape.Other examples of shape-memory material include shape memory polyurethane, crosslinking Horizontal polyoctenamer rubber, polynorbomene polymers, Nitinol, polyethylene, PMMA, polyurethane, crosslinked polyethylene, crosslinking are poly- different Pentadiene, the homopolymer of cyclo-octene, polylcaprolactone, (oligomeric) the copolymer of propyl propionate, PLLA, PL/DLA copolymer, PLLA PGA copolymers and other shapes memory material known to persons of ordinary skill in the art.

The other structure of first component

Fig. 6-1 and 6-2 illustrates another embodiment 58, wherein, the second buffer component includes two hydrogel contact lens 60, the two hydrogel contact lens 60 are attached to each other, to clamp the first rigid member between them.Fig. 6-1 is illustrated The embodiment 58 being arranged in ocular surface；Fig. 6-2 illustrates embodiment 58 before the disposing.In embodiment 58, first Component 62 is used as the skeleton of eye insert, and is used as drug delivering material.When tear fluid permeates hydrogel contact lens, it Contacted with first component, and medicine is eluted into tear fluid.Another embodiment (not shown) includes the outer structure of skeleton first Part, the outer skeleton first component include being attached to the drug delivering material on front side of contact lenses.Another embodiment (not shown) bag First component is included, the first component includes drug delivering material, and the drug delivering material is arranged on eyes and by common nothing Drug delivery contact lenses cover, to provide comfortable eyelid movement.

Second component

Fig. 7-1 illustrates the enlarged drawing of the example eye insert 31 of therapeutic system system 30, wherein, second component 34 is whole It is arranged in the peripheral length of first component 32.Second component 34 provides buffering, in order to which the extension of device is implanted into or is worn, It may be selected to be substantially prevented from the stimulation to eyes, to promote patient worn treatment system at least 30 days.Buffering effect can be at least Part obtained by the material used in second component, can also by the surface and/or edge shape of second component come Obtain.In certain embodiments, second component can include coating.

The material of second component is needed to be flexible, biocompatible and non-stimulated.The example of the material includes such as water Gel or silicone.

How are let it be overall shape and structure, and the edge of second component is usually formed as preventing in them and eyelid Rubbed between interior section.Fig. 7-2 illustrates the sectional view of therapeutic system system, and the therapeutic system system includes having wedge shape outer Portion and/or the second component 34 of internal edge 64.Fig. 7-3 illustrates the sectional view of therapeutic system system, the therapeutic system system Including the second component 34 with beveled edges 66.Fig. 7-4 illustrates the sectional view of therapeutic system system, the therapeutic system system Including the second component 34 with rounded edges 68.Fig. 8-1 illustrates the therapeutic system system 30 with second component 34, and this Two components can have preceding surface and/or rear surface 70, and the preceding surface and/or rear surface 70 can also form the curvature of eyes 70 partly Footpath.

In some embodiments 72, the second buffer component 74 is only arranged on some discrete portions along the length of first component Face in sharp edges or elbow, it is necessary to may stimulate the opening position of eyes.Fig. 9-1 illustrates the second buffer component 74, and this second Buffer component 74 is arranged in above the discrete portions of the length of the first supporting member 32.

Second component can also include coating, and the coating is arranged locally on second component, and the coating prevents otherwise can be swollen The second component expansion of swollen (can preferably be hydrated).Figure 10-1 and 10-2 illustrates embodiment 76, wherein, coating 78 is around second Component partial scatters, and is preferentially expanded in some regions for use in second component is enabled.Figure 10-1 is illustrated when coating ring Embodiment when being scattered around the part of second component 80, wherein first component 32 are in non-hydration status.Figure 10-2 illustrate Figure 10- 1 second component 80 hydration when (therefore in swelling state 76') embodiment.

In one embodiment, the first and second components can include similar with different hardness and/or further feature Component or material, particularly material can be handled, to there is the proper characteristics for the first and second components.

Drug delivery matrix

Conveying matrix is generally arranged, is embedded in, encapsulates or be otherwise contained in the medicine used in treatment system In.Conveying matrix may be embodied in the first frame member or the second buffer component or above them.Conveying matrix also includes can Biodegradable or non-biodegradable material.Conveying matrix can include polymer, but it is not limited thereto.Can biology Degradation polymer example include protein, hydrogel, polyglycolic acid (PGA), polylactic acid (PLA), poly- (L lactic acid) (PLLA), Poly- (L glycolics) (PLGA), PGA, poly- L lactides, poly- D lactides, poly- (amino acid), poly- dioxathion, in poly- caproic acid Ester, polydextrose acid, polylactic acid-polyethylene oxide copolymer, modified cellulose, collagen, poe, poly butyric, Polyanhydride, polyphosphoric acid esterase, poly- (α -ol acid) and combinations thereof.Not biodegradable condensate may include silicones, third Olefin(e) acid salt, polyethylene, polyurethane, polyurethane, hydrogel, polyester (such as,From E.I.Du Pont de Nemours and Company, Wilmington, Del), polypropylene, polytetrafluoroethylene (PTFE) (polytetrafluoroethylene (PTFE)), expanded PTFE Ethene (ePTFE), polyether etherketone (PEEK), nylon, extrusion collagen, polymeric foam shape thing, silicon rubber, poly terephthalic acid second Diol ester, high molecular weight polyethylene, polycarbonate urethane, polyurethane, polyimides, stainless steel, Ni-Ti are closed Gold (such as, Nitinol), titanium, stainless steel, cobalt-chromium alloy (such as,From Elgin Specialty Metals, Elgin, Ill；From Carpenter Metals Corp., Wyomissing, Pa.)。

In order to prevent an insert in potential allergic reaction in patient body, it is by including hypoallergenic original that eye insert, which needs, Material.Preferably, first and/or second component can include material such as hydrogel, polyethylene glycol (PEG) or polycyclic oxygen second Alkane (PEO), they prevent protein adherence, and therefore reduce and form anaphylactoid probability.Also may be selected, the medicine of eye insert Thing conveying matrix can include antiallergy and/or antihistaminic, to prevent the allergic reaction to eye insert.In some implementations In example, conveying matrix can also include other materials known in the art.

Treatment system medicine

Multi-medicament can send eyes to using treatment system.Preferably, these medicines are by including to the long-term of eyes Medicine needed for treatment.Needing the illness example of long-term treatment includes：Xerophthalmia, glaucoma, allergy, infection, bacterium, virus Infected with other, chronic inflammation symptom, such as acne rosacea keratitis, cyclitis and blepharitis, the retinal disorders of selection, such as Diabetic retinopathy, the symptom of the macular degeneration relevant with the age and other retinas, surgical site infections symptom, amblyopia Deng.

Some medicines for treating above-mentioned illness include：Steroids, antiinflammatory agents, antibiotic, glaucoma treatment chemical combination Thing, antihistaminic, dry eye drugs, neuroprotective agent, retinoids, anti-cardiovascular agents, antioxidant and bio-pharmaceutical.

The example of steroids includes glucocorticoid, progestational hormone, mineral corticosteroid or corticosteroid.The skin of example Matter steroid includes cortisone, hydrocortisone, prednisone, prednisolone, methyl prednisone, fluorine hydroxyl prednisolone, fluorine rice Dragon, dexamethasone, Medroxyprogesterone, betamethasone, Loteprednol, fluocinolone acetonide, aniprime, Rimexolone or Mometasone.Its Its steroids example includes androgen, such as testosterone, methyltestosterone or DANAZOL.

The example of antiinflammatory agents includes nonsteroid anti-inflammatory drugs (NSAID) such as piroxicam, acetylsalicylic acid, salsalate (Amigesic), diflunisal (Dolobid), brufen (Motrin), Ketoprofen (Orudis), Nabumetone (Relafen), piroxicam (Feldene), methoxy bitter edible plant propionic acid (aAleve, Naprosyn), Ciclofenaziae (Voltaren), disappear Scorching pain (indocin), Su Ling great (creosote), tolmetin (tolectin), according to Support degree acid (lodine), ketorolac (toradol) and pyrans (daypro) or 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-l-yl (celebrex).

The example of antibiotic include amoxycillin, penicillin, sulfa drugs, erythromycin, streptomysin, tetracycline, gram Erythromycin, terconazole, Azithromycin, bacitracin, cirramycins, evofloxacin, Ofloxacin, lavo-ofloxacin, not Husky star, gatifloxacin, aminoglycoside, tobramycin, gentamicin and polymyxin B combination are liked, it includes polymyxins B/ methoxybenzyl aminopyrimidines, polymyxin B/bacitracin, polymyxin B/neomycin/gramicidins.

Glaucoma includes Beta receptor blockers, for example, Timolol, betaxolol, Levobetaxolol and goat's rue Glycosides；Myotic such as pilocarpinum；Carbonic anhydrase inhibitor such as brinzolamide and Dorzolamide；Prostaglandin such as travoprost, Bimatoprost and Latanoprost；seretonergics；Choline medicine；Dopaminergic gaonist；Adrenergic gaonist Such as apraclonidine and Brimonidine；And prostaglandin or prostaglandin aids drug, such as Latanoprost, Bimatoprost Or travoprost.

Antihistaminic and columnar cell's stabilizer include olopatadine and epinastine, and acute treatment antiallergy product ketone is coughed up Sour trometamol, ketotifen fumarate, Loteprednol, epinastine HCl, Emedastine difumarate, nitrogen this Spit of fland hydrochloride, olopatadine hydrochloride, ketotifen fumarate；And chronic treatment antiallergy product includes croak sieve Come this potassium, sodium nedocromil, lodoxamide trometamol, nasmil.

Anti- cardiovascular agents include biological agent, ranibizumab (lLucentis) and bevacizumab (Avastin).Amblyopia medicine Thing includes anesthetic and cycloplegic, such as atropine.Dry eye drug includes cyclosporin.

The control of medicine elution process

Medicine elution can be controlled by the concentration of medicine be present, or by by medicine be embedded to or with various otherization Compound is combined to control.The special solubility characteristics (hydrophobicity or hydrophily) of medicine are fast by the elution for determining to control specific drugs The mode of rate.In some embodiments that medicine is hydrophobicity, medicine can be fine gtinding and to be dispersed to including silicone or polymerization In second buffer component of thing (such as hydrogel of high-hydrophilic).Hydrophilic medicament can be fixed on first component and (such as mould Material) or second component (such as hydrogel) in.Special selection for fixed polymer depends on medicine and its feature, closed The wall thickness of suitable elution speed and the coating comprising medicine (wall thickness can also change elution speed).For example, when medicine buries When entering in first polymer, the wall thickness speed that at least Partial controll medicine passes through of second polymer.On the contrary, the wall thickness of coating can For the Drug controlled release when medicine is embedded in frame element.

Other Considerations can include skeleton host material selection and medicine whether be included in skeleton in, skeleton Whether it is cast as special frame configuration and whether is coated with hydrogel or other polymer.

In hydrophobic drug, it can add comprising bile salt (deoxycholate, taurodeoxycholic acid salt and glycocholic acid Salt) or calcium chlorate surfactant (such as edta edta), to increase their solubility.

On the contrary, in order to reduce elution speed, drug particles can be coated, and can manufacture the lower soluble-salt of medicine Form, or rate limit coating, polymer or other materials may be embodied in conveying matrix and/or on conveying matrix, with Flowed out so that the resistance that the distance or material of medicine separating device pass through to medicine will limit medicine from device.

Whether other versions absorb enough water/tear fluids to force medicine to leave matrix, example including polymer Such as spongy or natural porous material, or material or other materials with artificially generated hole, the material be impregnated with so that Infiltration pumping effect must be produced.

The surface area and geometry for the treatment of system also can be used in controlling the elution speed of medicine.Therefore, treatment dress The geometry put can be designed so that tear fluid flows through the maximum flow or minimum for the treatment of system according to special requirement. For example, contact area of the increase surface area by increase between medicine and tear fluid.Whether suitable, dress if being conveyed according to target Put and msy be also constructed to so that it has bigger conveying area/surface area in bottom or top fornix.On the contrary, in order to reduce The elution speed of medicine, the contact area between eyes and drug particles will reduce.

Treatment system coating

In certain embodiments, second component also includes coating, further to relax the eyes of patient.Coating can wrap Include lubriation material, for example, from Biocoat, be based onHyaluronan coating.The advantages of Hydak, includes it Lubricity, biocompatible and high-hydrophilic in wetting, and can be applied using thin flexible coating, and it is biology The carrier of active material.Other coatings can also be included from SurModics (hydrophily or drug delivery) and Hydromer Hydrophily or drug delivery coating.

In order to easily carry out insertion process, some embodiments are coated, to cause an insert during insertion With firm quality.Once such eye insert arrangement is in place, coating will dissolve, so that eye insert becomes more easypro It is suitable, to use daily.

Treatment system is inserted and removed from

Treatment system can be arranged on eyes by doctor first, once the suitable drug delivery time cycle terminates, Then just removed by identical or different doctor from the preceding surface of eyes.Then, why doctor selectively can instruct patient Eye insert will be inserted and removed from by sample by he or she oneself.

The problem being inserted and removed from of device is held in the fine equilibrium between rigidity and flexibility.Too soft device will very Hardly possible insertion, and too hard device will be uncomfortable for wearing for a long time.

A kind of mode for the fine equilibrium being maintained between rigidity and flexibility is by by folding device or clamping into various Shape.Folding in a device more effectively keeps the structure of its shape by producing during insertion, therefore with being easier The ring structure of deformation, which is compared, to be had more preferable " pushability ".

It is to be folded with soluble material to hitch to insert and keep a kind of alternative of folding in a device, directly It is maintained to device in eyes.Soluble material enables to shape slowly to discharge cyclization.

Figure 11-1 illustrates annular eye insert 31, wherein, separate and/or relative part center close to or in The heart clamps, to form nonplanar taco (taco) shape 82.The ring device of clamping can be located so that one End can be in bottom or top eyelid slip underneath, and then, the other end can be positioned at below another eyelid.Figure 11-2 is illustrated Eye insert 31 when inserting on the surface of eyes, before soluble material allows slowly to be released back into annular；Figure 11-7 tables Show that the described device on the surface of eyes is in its fully expanded state 94.

Figure 11-3 illustrates one embodiment 84, wherein, annular shape includes serpentine shaped or a series of elbows, to cause Radially outer part or projection replace with radial inner portion.The embodiment has four projections, and produces clover blade shape, To cause four projections 86 each will to be conveniently arranged in the eyelid of upper and lower part and the temples of nose and eyes.This shape Interior section can also be by soluble material and keep together (or close to each other), but and does not need in this way, because energy Enough obtain good initial position.Figure 11-4 illustrates the embodiment 84 when inserting on the surface of eyes；Figure 11-7 tables Show that the described device in ocular surface is in fully expanded state 94.

Figure 11-5 illustrates alternative embodiment 88, wherein producing clover shape 90.In this example, top bump 92 is first Behind the eyelid of insertion top, then, two projections of bottom will be inserted behind the eyelid of bottom.It is identical with previous embodiment, This shape can also be held in place by soluble material, but and need not be in this way, because can obtain initial well Position.Figure 11-6 illustrates the described device when inserting on the surface of eyes；Figure 11-7 illustrates the institute in ocular surface State device and be in fully expanded state 94.

The insertion of device can also be facilitated by using conveying instrument.Figure 12-1 and 12-2 illustrates the promptly work of change Two alternatives of tool 150 and 160, its further groove or groove 170 are in end, in order to the promptly device.Preferably, pawl is oriented Preceding distal surface, the distal surface have the top layers for example including silicone or Teflon, if to cause they and eyes Surface contacts, and is wiped one's eyes if they will not be scraped.In Figure 12-2, the transferring instrument that can accommodate two or more pawls is illustrated The embodiment of device, preferably three or four pawls 162 (in order to which simplification illustrates two pawls in figure), when device 160 is clamped in ring When upper, these pawls 162 produce clover or bunge bedstraw herb shape.Three or four pawls 162 are drawn close simultaneously by exterior tube, and this compels Pawl is set to be compressed from their more loose external positions.

Figure 12-3 to 12-5 illustrates the different embodiments of the pawl 162 of promptly instrument, and these, which are firmly grasped instrument and are changing into, has Special shape on groove, to help folding device into the shape of the form fit with eye.Figure 12-3, which is illustrated, to be had The pawl of groove 172, the groove 172 extend horizontally across pawl.Figure 12-4 illustrates the pawl with groove 175, and the groove 175 is bending, with Just so that ring bends to the shape being easily consistent with the shape of eyes.

Figure 12-5 illustrates the alternative embodiment of the pawl with curved slot 176.In this embodiment, pawl, which includes three, has The adjacent sheet of level trough.As shown in Figure 12-5, in order to catch annular eye insert 31, middle sheet 178 somewhat raises, so as to The curved slot for ring material can be formed.As shown in Figure 12-6, in order to discharge an insert 31, once the protrusion of ring folds Contacted with ocular surface, middle sheet pushes down on, to cause all sheets to be all mutually aligned, in the sidepiece extension of three sheets Groove be at this moment it is horizontal, at this moment, ring will easily from promptly instrument discharge.

Figure 13-1 to 13-4 illustrates the optional mode that ring discharges from promptly instrument.Figure 13-1 illustrates the promptly work of change Tool 160, promptly should include four pawls 162 by instrument 160, each pawl includes being located at the groove 170 at its front end, and the groove 170 is towards grabbing The center of clamping tool.Figure 13-2 illustrates the promptly instrument 160 of change, and should firmly grasping instrument 160, promptly eye is inserted in groove 170 Enter part 31, pawl 162 is fastened on insert, so as to produce four projections, so as to which eye insert easily to be inserted to the eye of patient Posterior surface of eyelid.Once the protrusion folding part of ring device is had been arranged on eyes, there is each rotation 180 of arm of pawl^o, to cause groove Not along the neighboring arrangement of promptly instrument；At this moment, the ring of folding can be easy to skid off, because they are no longer held in groove In.Figure 13-3 illustrates the promptly instrument 160 of change, wherein, each pawl has been rotated by about 180^o, to cause each groove 170 at this moment Face away from the center of promptly instrument.Groove rotates 180^oIt will cause to discharge eye insert 31.Figure 13-4 illustrates grabbing from change The eye insert 131 discharged on clamping tool 160.

Figure 14-1 to 14-5 is illustrated can screening device and the method for inserting ring device.Figure 14-1 illustrates injection Device shape dress puts 180, and the syringe shape dress, which puts 180, to be included：Cylinder 182, the cylinder 182 has flat tip 184, can promote an insert 31 pass through the flat tip 184；And plunger 186.In order to which ring device is inserted in syringe, the plunger of syringe is extracted, Ring device is folded into flat, and inserts in the body of syringe, plunger is put back in syringe.Figure 14-2 illustrates note Emitter shape dress puts 180, wherein, eye insert be folded into it is flat, and in insertion tube 182.In the insertion tube of plunger 186, and cylinder Including tube chamber, open pointed tip includes mouth, and insert 31 can be promoted to pass through the mouth.In order to which ring device is inserted in eyes, post In the body of plug push-in syringe, so that ring device is slowly pressed through the flat tip of syringe.Figure 14-3 tables Shown substantially from syringe shape dress put 180 the extrusion of tip 184 and prepare to be arranged in the episcleral eye insert 31 of eyes Ring.Figure 14-4 illustrates the ring for the episcleral eye insert 31 for being arranged locally on eyes；Its remaining part of eye insert will be promoted 180 tip 184 point is put by syringe shape dress, and on release to eyes.Figure 14-5, which is illustrated, to be arranged on the sclera of eyes Eye insert 31.

Figure 15-1 to 15-3 illustrates another optional eye insert insertion apparatus of similar classical bicycle loudspeaker.Figure 15-1 The tubaeform insertion apparatus 180 of bicycle is illustrated, the insertion apparatus 180 includes two parts：Loudspeaker 182 and extrusion ball 184.Figure 15-2 illustrates the enlarged drawing of loudspeaker 182.Loudspeaker include flexible material 182, have conduit 188, and the conduit 188 causes extrusion ball It is connected with the outer rim of insertion apparatus.The outer rim of loudspeaker includes groove 186, and the groove 186 is sized to coordinate with ring device.Figure 15-3 illustrates the sectional view of the tubaeform insertion apparatus of bicycle, and the insertion apparatus includes loudspeaker and extrusion ball.Extrusion ball includes Vacuum source and the holder for liquid 190 (preferably salt solution).Extrusion ball is arranged on loudspeaker.

In order to pick up ring device to be inserted on the surface of eyes, extrusion ball is extruded, so as to produce vacuum Sealing, the vacuum sealing will be picked up ring device and maintained it in the groove of the outer rim of loudspeaker.In order to which ring device is arranged On the preceding surface of eyes, loudspeaker are gently inserted below two eyelids of eyes, and somewhat extrude the extrusion ball, so as to So that liquid flows through the conduit of loudspeaker from the holder of extrusion ball, it is true between ring device and the outer rim of loudspeaker so as to destroy Sky sealing.Then, gently loudspeaker are pulled out below eyelid.

Figure 16-1 to 16-6 illustrates optional insertion apparatus 192.Figure 16-1 illustrates optional insertion apparatus 192, and this is inserted Entering device 192 includes flexible cone 194, and outer rim 196 of the cone 194 along it supports ring device, and the figure also illustrates use Eye insert is arranged in the method on the sclera 8 of eyes 2 by it.Figure 16-2 illustrates the amplification of the outer rim of conveying device 196 Figure.Outer rim includes being designed to the groove 198 coordinated with annular eye insert 31.Figure 16-3 illustrates the insertion dress including flexible cone Put 192 front view.Flexible cone includes two slits 198, so as to change the diameter of cone.Figure 16-4 to 16-6 is represented Method that an insert 31 is inserted using insertion apparatus 192.Figure 16-4 illustrates the insertion equipped with annular eye insert 31 Device 192, this insert 31 are gently squeezed into below top eyelid 202 and bottom eyelid 204.Figure 16-5 illustrates clamping Or the flexible cone 194 pulled, to reduce the periphery of cone, and annular eye insert 31 is discharged from the outer rim 196 of cone.Figure 16-6 illustrates the annular eye insert 31 stayed in eyes, and cone 194 pulls away below eyelid.

Figure 17-1 to 17-2 illustrates optional insertion apparatus.Figure 17-1 illustrates the insertion for including flexible bending band 208 Device 206.As shown in Figure 17-2, curved bel includes curved slot, and the curved slot can support an insert 31, while eye inserts Part is gently slid into behind at least one eyelid.

Example 1：For calculating-olopatadine of the drug therapy effective dose of eye insert

Below by by demonstrating the administration that can be used for according to medicine for treating the medicine olopatadine of allergic condition Area for treatment and the method for calculating the effective equipment delivered dose for the treatment of of medicine.Computational methods comprise the following steps：1) determine every The suitable drop number of secondary application；2) drop number is caused to be multiplied by 30uL (volume of a drop)；3) the solid drugs amount per uL is determined；4) cause The result of step 2 is multiplied by the result of step 3, to find the solid drugs amount that be applied to eyes daily；5) step 4 is caused As a result it is multiplied by the number of days for wishing to be treated with the specific drugs；And 6) it is multiplied with drug delivery efficiency.Final quantity preferably will be from Eye insert diverging.

Olopatadine is a kind of eye antihistaminic (H I- receivers) and columnar cell's stabilizer.Olopatadine it is common into Year people's dosage for example can be a drop (when using 0.1% solution) and each in each impacted eyes twice daily A daily drop in impacted eyes (when using 0.2% solution).

When the olopatadine solution of estimated service life 0.1%, 1mL medicine corresponds to 1mg medicine.One drop is 30uL, This is corresponding to 0.03mL solution and 30ug olopatadine.Because 0.1% solution is applied twice per day, therefore olopatadine Daily dosage be 60ug.Because eye drops is poorly efficient in drug delivery, the 90-95% quilts of the olopatadine of eyes are applied to Wash away.This leaves behind 3-6ug olopatadine in eyes.Daily for 3-6ug, the amount for 30 days is about 90-180ug Olopatadine, it can be conveyed to an eyes within the time of one month.

Example 2：Drug delivery processing procedure and elution speed control-olopatadine hydroxide for hydrophilic medicament

Olopatadine HCl (OH) for ophthalmically acceptable way can be configured to 0.2% (2mg/mL) solution.Include 100ug OH's 50uL it is mono- drop can be once a day instillation eyes in and continue 2 weeks.When estimating 5% availability, the agent of 5ug/ days is provided Amount is conveyed to barrier film, the 70ug altogether during treatment in 2 weeks.By using barrier film (such as HEMA, PVA, PVP, GMA, cellulose dialysis Pipe etc.) medicament reservoir is separated or medicine is embedded in implantation piece and at least 70ug of dry form is loaded into implantation piece In and be discharged into tear film.Rate of release can by change be exposed to tear film in surface area, by changing medicine Release control barrier film etc. controls, to adjust to suitable 5ug/ days (0.21ug/ hours).Assume 100% in the calculation again Target dose all reach its target location, and do not washed away, more accurately calculated possibly also with washing away data by tear film Come carry out.

For two examples, the medicine for example for being directly administered during hydration-treated is coated with the outside of implantation piece Ball, therefore medicine can cross barrier film or be flowed through holder.These coatings can be into (such as forming sediment with being easily dissolved layer Powder, sugar) solid drug forms, to keep so that solid drugs are arranged in the outside of implantation piece.

Example 3：Drug delivery processing procedure and elution speed control-predniso lone acetate for hydrophobic drug

Generally, 1% predniso lone acetate suspension (10mg/mL) is 2 drop (about 100uL volumes altogether) 4 times daily, And continue one week.The dosage of estimation 5% is actually available to be absorbed into cornea, and the amount is the predniso lone acetate of 20ug/ days.This Sample, one week can be 140ug with dosage.Solubility into the predniso lone acetate of the aqueous solution is approximate 240ug/mL.At least 140ug Solid predniso lone acetate can be fitted into implantation piece so that predniso lone acetate is with the speed of about 0.83ug/ hours Rate is dissolved in tear layer.The speed can be by controlling the porosity of implantation piece and the surface area in tear film To control.

For these simplification calculate, it is assumed that 100% dosage is in target (cornea) position and is absorbed completely, not due to Loss is produced from the tear layer that cornea flows away.Regulation can be carried out based on test data, modeling etc..

Although describing example embodiment in slightly greater detail by example embodiment, those skilled in the art should A variety of changes, improvement and change can be carried out when knowing.Therefore, the scope of the present invention limits simply by accessory claim System.

Claims (16)

1. An a kind of 1. insert, in eyes, eyes to have the top eyelid that can extend along anterior ocular surface and lower eye Eyelid, and have visual zone between them, the insert includes：

   First component, the first component include annulus, and the first component can be along the preceding surface layout of the eyes of patient in visual area The outside in domain；

   Second component, the second component are supported by first component, and are arranged in along the length of first component above discrete portions；With And

   At least one of conveying matrix in second component medicine, safety and to be controlled in more days every day At least one medicine for treating effective dose is released to eyes from second component, and

   Wherein, activated after eye insert is configured on the preceding surface for be inserted into eyes to be re-configured to open up from insert structure Opening structure, make the first component of an insert and second component consistent with the preceding surface of eyes, so as to make insert keep with More days of eye contact.
2. 2. according to claim 1 insert, wherein：The second component is configured to delay between first component and eyes Punching engagement, to prevent from stimulating eyes when first component assists in keeping more days of insert and eye contact.
3. 3. according to claim 1 insert, wherein：Insert has the anti-repulsion shape of annular, has rear surface, preceding Surface and radially extending inside edge and outer ledge between rear surface and preceding surface, the rear surface is used for and eyes The engagement of preceding surface, periphery extension of the first component along annular shape, so as to the shape of abundant retaining ring band, so as to by insert Capture between top eyelid and the preceding surface of eyes, and between bottom eyelid and the preceding surface of eyes, second component cloth Put between first component and eye tissue, eye tissue includes sclera and/or at least one eyelid.
4. 4. according to claim 1 insert, wherein：Include at least 30 days within this more days.
5. 5. according to claim 1 insert, wherein：Conveying at least one of matrix medicine is included from the following group The one or more of selection, the group include：

   Steroids, antiinflammatory agents, antibiotic, glaucoma therapeutics compounds, antihistaminic, anti-cardiovascular agents, bio-pharmaceutical and/or Xerophthalmia compound.
6. 6. according to claim 1 insert, wherein：Conveying at least one of matrix medicine is included from the following group The one or more of selection, the group include：

   Steroids, including glucocorticoid, progestational hormone, mineral corticosteroid, corticosteroid；Corticosteroid include can Pine, hydrocortisone, prednisone, prednisolone, methyl prednisone, fluorine hydroxyl prednisolone, fluorometholone, dexamethasone, first hydroxyl Progesterone, betamethasone, Loteprednol, fluocinolone acetonide, aniprime, Rimexolone, Mometasone, androgen, testosterone, methyl testis Sterone and/or DANAZOL；

   Nonsteroid anti-inflammatory drugs, including piroxicam, acetylsalicylic acid, salsalate (Amigesic), diflunisal (Dolobid), brufen (Motrin), Ketoprofen (Orudis), Nabumetone (Relafen), piroxicam (Feldene), methoxy bitter edible plant propionic acid (aAleve, Naprosyn), Ciclofenaziae (Voltaren), indocin, Su Ling great, toluoyl Pyridylacetic acid, Etodolac (Lodine), ketorolac (Toradol) and pyrans (Daypro), and/or 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-l-yl (Celebrex)；

   Antibiotic, including amoxycillin, penicillin, sulfa drugs, erythromycin, streptomysin, tetracycline, clarithromycin, spy Health azoles, Azithromycin, bacitracin, cirramycin, evofloxacin, Ofloxacin, lavo-ofloxacin, do not like husky star, plus replace Sha Xing, aminoglycoside, tobramycin, gentamicin, polymyxin B combination, polymyxin B/methoxybenzyl aminopyrimidine, more Acarasiales Plain B/ bacitracins, and/or polymyxin B/neomycin/gramicidins；

   Glaucoma, including Beta receptor blockers, Timolol, betaxolol, Levobetaxolol, galutedin, miosis Medicine, pilocarpinum, carbonic anhydrase inhibitor, brinzolamide, Dorzolamide；Prostaglandin, travoprost, Bimatoprost, Latanoprost；seretonergics；Choline medicine；Dopaminergic gaonist；Adrenergic gaonist, apraclonidine, bromine Mo Niding, prostaglandin or prostaglandin aids drug, Latanoprost, Bimatoprost and/or travoprost；

   Antihistaminic and columnar cell's stabilizer, including olopatadine and epinastine, acute treatment antiallergy product, ketorolac Trometamol, ketotifen fumarate, fluorine replace sprinkle promise, epinastine HCl, Emedastine difumarate, nitrogen grass this Spit of fland hydrochloride, olopatadine hydrochloride, ketotifen fumarate, chronic treatment antiallergy product, pemirolast Potassium, sodium nedocromil, lodoxamide trometamol, nasmil；And/or

   Treat dry eyes eyeball compound, including cyclosporin.
7. 7. according to claim 1 insert, wherein：It is hydrophilic to convey at least one of matrix medicine, and Medicine is dispersed in hydrophilic polymer.
8. 8. according to claim 1 insert, wherein：It is hydrophobicity to convey at least one of matrix medicine, and Insert includes being used for the soluble surfactant for increasing medicine.
9. 9. according to claim 1 insert, wherein：It is hydrophobicity to convey at least one of matrix medicine, and Insert includes elution rate reduction material, and the elution rate reduction material is included in coating above medicine, conveying matrix group Point and/or conveying matrix on coating.
10. 10. according to claim 1 insert, wherein：The annulus has the part selected from the following group：

    Two projections, the two projections extend radially outwardly from annulus, to be engaged in blink with eyelid and to determine insert Position cyclization is around visual zone；

    Along at least one of partial thickening of annulus；

    The multiple haptic elements radially extended from annulus；

    At least one circular arc, the circular arc and annulus radial deflection；And

    Multiple radial components, these radial components extend between at least one circular arc and annulus；Or

    Radial inner portion, the radial inner portion and radially outer part dispersed placement.
11. 11. according to claim 1 insert, wherein：The annulus has an inward flange and outward flange, and at least one in edge It is individual that there is antisitic defect shape, to avoid the sharp edges of eyes from stimulating.
12. 12. according to claim 1 insert, wherein：The annulus has non-planar shaped eyes composition surface.
13. 13. according to claim 1 insert, wherein：Second component expands in hydration, and also includes being arranged in the One and second component above a series of separated anti-expansion bands.
14. 14. according to claim 1 insert, wherein：Using that can drive conveying instrument, this can drive conveying instrument to have Receiver, for releasedly receiving insert, to support the insert in the position fixing process of insert, convey instrument Driving allows at least a portion of insert to be engaged with eyes between sclera and eyelid, atraumatically to be released from receiver Put insert.
15. 15. according to claim 1 insert, wherein：At least one of conveying matrix medicine is controlled including blepharitis Treat compound.
16. 16. according to claim 1 insert, wherein：Design second component surface area and/or geometry with Just the elution speed of at least one of control conveying matrix medicine.